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Grape seed extract halts cell cycle, checking growth of colorectal tumors in mice

cer cells.

In this study, Agarwal tested the extract on colorectal cancer, the second most common malignancy in Americans as well as the second leading cause of cancer deaths in this country. They exposed two different human colon carcinoma cells to the extract, and found a dose- and time-dependent inhibition of cell growth.

"Beneficial effects were correlated with how much extract was used and how long it was used for," Agarwal said. The number of live cells decreased by 92 percent in one cell line when the highest dose was given for the longest time period, which was two days, he said.

The researchers then performed a cell cycle distribution analysis, looking to see specific growth inhibitory effects. They found that the longer the extract was used, the more cells were "arrested" in the G1 phase of the cell cycle, the time when the cell is preparing to duplicates its DNA before dividing, and, correspondingly fewer cells had advanced to the "S" phase, when DNA is being actively duplicated.

They then studied the extract's effect on the molecular regulators that control the cell cycle, and found a strong dose-dependent increase in Cip1/p21 protein. In fact, the amount of Cip1/p21 protein within the cells increased by more than 150 times after 12 hours of treatment, Agarwal said. The researchers also noted a corresponding decrease in a number of different cyclin proteins and associated cyclin-dependent kinases (CDKs).

This all makes sense, according to Agarwal. One of the hallmarks of cancer is rampant cell growth due to loss of control of the cell cycle, and CDKs help push the cycle from a quiet state through to cell division. The Cip1/p21 protein, however, is powerful enough to inhibit the activity of CDKs and can also control apoptosis, or programmed cell death, he said.

"This protein physically interacts with CDKs," Agarwal said. "In normal cells, it attaches to CDKs to inhibit growth, but if a cell wants t
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Contact: Warren Froelich
froelich@aacr.org
215-440-9300
American Association for Cancer Research
18-Oct-2006


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